Review of metastatic colorectal cancer treatment pathways and early clinical experience of trifluridine/tipiracil in the UK named patient programme

Abstract

Background: The standard first-and second-line chemotherapy backbone regimens for metastatic colorectal cancer (mCRC) are 5-fluorouracil (5-FU)/capecitabine-based with addition of irinotecan or oxaliplatin. Until recently, evidence for optimal sequencing post second-line was sparse. Trifluridine/tipiracil (indicated for mCRC and gastric cancer after standard chemotherapies) was made available to UK patients via a named patient programme (NPP) before receiving marketing authorisation in Europe in 2016, allowing characterisation of UK treatment pathways, and evaluation of trifluridine/tipiracil in a UK non-trial population.Methods: Data collected routinely for the NPP were analysed to describe the patient demographics, clinical characteristics and treatment pathways. Patients eligible for the programme were adults (≥18 years) with histologically or cytologically confirmed mCRC who had previously received chemotherapy treatment(s).Results: Of the 250 eligible patients enrolled in the NPP, 194 patients received ≥1 dose of trifluridine/tipiracil and 56 patients did not receive trifluridine/tipiracil. The following results are reported first for patients who received trifluridine/tipiracil and second for those who did not receive trifluridine/tipiracil: median (IQR) age was 63.0 (54.0-69.0) and 62.0 (54.8-69.0) years; Eastern Cooperative Oncology Group performance status score was 0 for 28 and 14%, 1 for 65 and 70%, 2 for 7 and 16%. In terms of previous systemic treatments 47 and 43% had 2 prior lines of therapy. FOLFOX-, FOLFIRI-and CAPOX-based therapies were the most common first-line regimens in patients receiving trifluridine/tipiracil (37, 35 and 21%, respectively), and in patients not receiving trifluridine/tipiracil (41, 30 and 20%, respectively). Second-line treatment regimens in patients receiving and not receiving trifluridine/tipiracil were most commonly FOLFIRI-based (48 and 41%, respectively) and respectively). Patients received a median of 2 cycles of trifluridine/tipiracil with a median treatment duration of 1.8 (95% CI: 1.8-2.4) months. In patients who discontinued treatment due to disease progression, the median progression-free duration was 2.8 (95% CI: 2.4-2.9) months. Conclusions:The results highlight the number of treatment pathways used to treat mCRC in routine UK clinical practice prior to the marketing authorisation and National Institute for Health and Care Excellence approval of trifluridine/tipiracil and highlight the lack of clinical guidelines for mCRC.

Trifluridine/Tipiracil in Metastatic Colorectal Cancer: A UK Multicenter Real-world Analysis on Efficacy, Safety, Predictive and Prognostic Factors

“…Several other real-world studies assessing trifluridine/tipiracil in mCRC have also included patients with ECOG PS 2. [10][11][12][13][14][15] Our findings are keeping with the existing literature showing that patients with borderline performance status do not experience added toxicity from trifluridine/tipiracil 12 but seem to have worse survival outcomes. 11,13,14 The type of previous lines of treatment was another point of divergence between our study and the RECOURSE trial.…”

“…These findings are consistent with several other real-world studies. [10][11][12]15,20 The use of granulocyte colony stimulating factor was found to vary among different centres and is at the discretion of the treating physician. The most frequent non-haematological toxicities were fatigue and gastrointestinal symptoms such as nausea, diarrhoea and vomiting and were mild in the vast majority of patients both in the real-world and trial setting.…”

Efficacy and tolerability of trifluridine/tipiracil in patients with refractory metastatic colorectal cancer at the general hospital of Šibenik-Knin country

“…The improved treatment outcomes in randomized trials are sometimes hard to achieve in everyday clinical practice; thus, observational studies and retrospective analyses are often needed to assess the effects of anti-cancer drugs in the real-life setting. In clinical trials TT demonstrated a beneficial effect on PFS and OS in patients with mCRC refractory to standard chemotherapy (9)(10)(11)(12)(13)(14)(15). In randomized phase III clinical trial (RESOURCE)…”

Thymoquinone chemosensitizes human colorectal cancer cells to imatinib via uptake/efflux genes modulation

“…It is considered the fourth leading cause of cancer‐related deaths across the world according to the World Health Organization (WHO) 2 . Because it became a necessity to improve the prognosis of CRC patients, accordingly the search for combinational therapeutic strategies evoked to be a demanding need aiming to increase the curing rate of the disease 3 …”